Kimura Disease: An Unusual Presentation of Parotid Mass in a Sickle Cell Disease Patient.

Kimura disease (KD) is a rare benign chronic inflammatory condition of unknown cause, usually affecting young men of the Asian race. It is frequently associated with nephrotic syndrome. In this report, we present an uncommon case of KD in a 40-year-old Saudi man with sickle cell disease who presented with swelling on the right side of his face. CT scan of the head and neck showed the asymmetrical appearance of both parotid glands: the right side appeared heterogeneously enlarged, with adjacent moderate-to-significant fat stranding. Histologically, hyperplastic changes in lymphoid tissue were observed. The patient underwent superficial parotidectomy and was then followed up till the healing of the surgical site with no complications.

The Prevalence of Depression and Anxiety in Post-bariatric Surgery Patients at King Khalid University Hospital, Riyadh.

Background Obesity negatively impacts mental and physical health and is a leading cause of disease worldwide. Obesity affects 33% of Saudi adults, with 10% being morbidly obese (body mass index, BMI >40 kg/m2). This study explored the association between bariatric surgery (BS) and a predisposition or exacerbation of depressive and anxiety symptoms. Material and methods A cross-sectional study of patients who underwent bariatric surgery at the King Khalid University Hospital in Riyadh, Saudi Arabia, was conducted between February 2016 and December 2021. The patients were contacted by phone to complete a self-administered questionnaire on demographic information, chronic medical diseases, psychiatric diseases, body mass index, and type of bariatric surgery. In addition, they completed the patient health questionnaire-9 (PHQ-9) and general anxiety disorder-7 (GAD-7) questionnaire to screen for patients' depression and anxiety symptoms. Results The findings of the 367 BS patients showed that 20.7% of the patients were considered to have mild anxiety, 11.2% had moderate anxiety, and 8.7% had high anxiety levels. However, regarding depression, 46.9% had extremely low levels of depression, followed by mild depression in 29.4% and moderate depression in 11.2%. Furthermore, another 8.2% of BS patients had moderately high depression levels, and 4.4% had severe depression. The anxiety and depression levels of the patients in this study did not show any statistically significant changes postoperatively in the short, medium, or long term. On the other hand, almost all of the patients 97% who underwent bariatric surgery were satisfied with the outcome of their surgery. Conclusion Few BS patients had high symptoms of depression and anxiety. We recommend pre- and postoperative psychiatric assessment for all bariatric surgery patients as surgical protocol.

Diagnostic Reliability of Ultrasound Compared to Magnetic Resonance Cholangiopancreatography and Endoscopic Retrograde Cholangiopancreatography in the Detection of Obstructive Jaundice: A Retrospective Medical Records Review.

Background Challenges in the diagnosis of obstructive jaundice include locating the level of obstruction, knowing the cause of obstruction, and differentiating between benign and malignant causes. Imaging plays a significant role in detecting the causes of obstruction. Radiologists aim to diagnose biliary obstruction, its level, extent, and probable causes to determine the appropriate treatment for each case.  Methods Our study is a retrospective medical record review study. It included 150 patients who had ultrasound (US) diagnosis of biliary obstruction and underwent magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) in King Fahad Specialist Hospital, Buraidah. The patients' medical records have been reviewed to measure the sensitivity and specificity of US, MRCP, and ERCP.  Results Statistical analysis of the data showed that the sensitivity of US in detecting the most common cause of biliary obstruction, common bile duct (CBD) stone, was 26.6%, while the specificity was 100%. Comparing this sensitivity of US in detecting CBD stones to that of MRCP and ERCP, we obtained the following: US, 26.6%; MRCP, 62.9%; and ERCP, 62.4%. Although US was the least sensitive for detecting CBD stones, its specificity in this detection was 100%, while MRCP was 63.6%, and ERCP was 55.2%. Conclusion  US is the best initial step for the diagnosis of biliary obstruction. However, MRCP and ERCP are more sensitive in detecting CBD stones compared to US. Also, compared to US, they have shown higher percentages in all aspects of detection: level, cause, and extent of biliary obstruction.

Defining optimal dosing of ciprofloxacin in patients with septic shock.

BACKGROUND: Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics. OBJECTIVES: To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients. METHODS: Adult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio >125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa. RESULTS: We included 48 patients with median Simplified Acute Physiology Score (SAPS) II of 49 and 90 day mortality of 33%. Ciprofloxacin pharmacokinetics was best described by a two-compartment linear model including CLCR and body weight as covariates on CL and central volume respectively. With a dose of 400 mg q8h and CLCR of 80 mL/min, >95% PTA was achieved for bacteria with MICs ≤0.25 mg/L. For empirical treatment of P. aeruginosa, 600 mg q8h only reached a maximum of 68% FTA. For directed therapy against P. aeruginosa, a dose of 600 mg q8h was needed to achieve sufficient AUC/MIC ratios. CONCLUSIONS: In patients with septic shock, standard ciprofloxacin dosing achieved concentrations to successfully treat bacteria with MICs ≤0.25 mg/L and then only in patients with normal or reduced CLCR. To cover pathogens with higher MICs or in patients with augmented renal CL, doses may have to be increased.

Protective potential of thymoquinone against peroxynitrite induced modifications in histone H2A: In vitro studies.

Peroxynitrite (ONOO-) is a reactive oxidant involved in numerous pathological conditions. Thymoquinone (TQ) is an active constituent of Nigella sativa and is reported to have anti-disease activities, but its role on ONOO- has never been investigated. This study was undertaken to investigate the role of TQ on ONOO--induced damage of histone-H2A. Our novel data showed TQ significantly inhibited ONOO--induced oxidative damage in histone-H2A. ONOO- induces UV-hypochromicity of histone-H2A, whereas TQ reversed this effect to hyperchromicity. Tyrosine fluorescence was significantly reduced by ONOO- and was significantly increased upon TQ treatment. TQ reduces ONOO--induced hydrophobicity in histone-H2A and also reduces thermal stability of ONOO--histone H2A complex. SDS-PAGE of native histone-H2A showed a single band, which disappeared when treated with ONOO- alone. This changed was retained when protein samples were treated with TQ. Similar protective effects of TQ were found when protein carbonyl contents were estimated. In conclusion, this is the first study that shows the potential of TQ against ONOO--induced damaged of histone-H2A. TQ inhibits oxidative modification of tyrosine, lysine, arginine, proline and threonine in histone-H2A. These results have importance for the development of novel therapeutic strategies for the treatment of disorders, where ONOO- plays a role.

Maximally effective dosing regimens of meropenem in patients with septic shock.

OBJECTIVES: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. METHODS: Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method. Monte Carlo simulations were employed to define optimum dosing regimens for treatment of empirical or targeted therapy of A. baumannii and P. aeruginosa. EudraCT-no. 2014-002555-26 and NCT02240277. RESULTS: Fifty patients were included, 26 male and 24 female, with a median age of 64 years with an all-cause 90 day mortality of 34%. A two-compartment linear model including creatinine clearance (CLCR) as a covariate best described meropenem pharmacokinetics. For empirical treatment of A. baumannii, 2000 mg/6 h was required by intermittent (30 min) or prolonged (3 h) infusion, whereas 6000 mg/day was required with continuous infusion. For P. aeruginosa, 2000 mg/8 h or 1000 mg/6 h was required for both empirical and targeted treatment. In patients with a CLCR of ≤ 100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h. CONCLUSIONS: In patients with septic shock and possible augmented renal clearance, doses should be increased and/or administration should be performed by prolonged or continuous infusion to increase the likelihood of achieving therapeutic drug concentrations. In patients with normal renal function, however, standard dosing seems to be sufficient.

Population Pharmacokinetics of Tigecycline in Critically Ill Patients with Severe Infections.

We sought to describe the population pharmacokinetics of tigecycline in critically ill patients and to determine optimized dosing regimens of tigecycline for different bacterial infections. This prospective study included 10 critically ill patients given a standard dose of tigecycline. Blood samples were collected during one dosing interval and were analyzed using validated chromatography. Population pharmacokinetics and Monte Carlo dosing simulations were undertaken using Pmetrics. Three target exposures, expressed as ratios of the 24-h area under the curve to MICs (AUC0-24/MIC), were evaluated (≥17.9 for skin infections, ≥6.96 for intra-abdominal infections, ≥4.5 for hospital-acquired pneumonia). The median age, total body weight, and body mass index (BMI) were 67 years, 69.1 kg, and 24.7 kg/m2, respectively. A two-compartment linear model best described the time course of tigecycline concentrations. The parameter estimates (expressed as means ± standard deviations [SD]) from the final model were as follows: clearance (CL), 7.50 ± 1.11 liters/h; volume in the central compartment, 72.50 ± 21.18 liters; rate constant for tigecycline distribution from the central to the peripheral compartment, 0.31 ± 0.16 h-1; and rate constant for tigecycline distribution from the peripheral to the central compartment, 0.29 ± 0.30 h-1 A larger BMI was associated with increased CL of tigecycline. Licensed doses were found to be sufficient for Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus for an AUC0-24/MIC target of 4.5 or 6.96. For a therapeutic target of 17.9, an increased tigecycline dose is required, especially for patients with higher BMI. The dosing requirements of tigecycline differ with the indication, with pathogen susceptibility, and potentially with patient BMI.

Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients.

The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h-1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h-1 A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.

Tubo-ovarian abscess in non sexually active adolescents.

A tubo-ovarian abscess is a rare presentation in non-sexually active adolescents; only 11 cases have been reported in the literature. Variable approaches for diagnosis and management are described. We present a 19-year-old, non-sexually active, medically free girl, who had an abdominopelvic mass with abdominal pain and vomiting followed by fever. She had a confusing presentation of malignancy versus tuberculosis, with the help of imaging, diagnosis and treatment with percutaneous drainage, conservative treatment was achieved. Diagnosis of a tubo-ovarian abscess is difficult in non-sexually active adolescents, a high clinical index of suspicion is important as misdiagnosis may lead to radical and aggressive management, conservative management is possible in many of these patients.

Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients.

Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (≥40 kg/m2). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (n = 6) and morbidly obese (n = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m2, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (Vc) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m2 A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.

Effect of Obesity on the Population Pharmacokinetics of Meropenem in Critically Ill Patients.

Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m(2)), obese (30.0 to 39.9 kg/m(2)), and morbidly obese (≥40 kg/m(2)). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean ± standard deviation (SD) age, weight, and BMI were 49 ± 15.9 years, 95 ± 22.0 kg, and 33 ± 7.0 kg/m(2), respectively. A two-compartment model described the data adequately. The mean ± SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 ± 6.0 liters/h; volume of distribution in the central compartment (V1), 11.7 ± 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 ± 35.1 liters h(-1); and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 ± 12.24 liters h(-1) Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V1, dose adjustment based on CLCR appears to be more important than patient BMI.

Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: A structured review.

The increased prevalence of obesity presents challenges for clinicians aiming to provide optimised antimicrobial dosing in the intensive care unit. Obesity is likely to exacerbate the alterations to antimicrobial pharmacokinetics when the chronic diseases associated with obesity exist with the acute pathophysiological changes associated with critical illness. The purpose of this paper is to review the potential pharmacokinetic (PK) changes of antimicrobials in obese critically ill patients and the implications for appropriate dosing. We found that hydrophilic antimicrobials (e.g. ß-lactams, vancomycin, daptomycin) were more likely to manifest altered pharmacokinetics in critically ill patients who are obese. In particular for ß-lactam antibiotics, obesity is associated with a larger volume of distribution (V(d)). In obese critically ill patients, piperacillin is also associated with a lower drug clearance (CL). For doripenem, these PK changes have been associated with reduced achievement of pharmacodynamic (PD) targets when standard drug doses are used. For vancomycin, increases in Vd are associated with increasing total body weight (TBW), meaning that the loading dose should be based on TBW even in obese patients. For daptomycin, an increased Vd is not considered to be clinically relevant. For antifungals, little data exist in obese critically ill patients; during fluconazole therapy, an obese patient had a lower V(d) and higher CL than non-obese comparators. Overall, most studies suggested that standard dosage regimens of most commonly used antimicrobials are sufficient to achieve PD targets. However, it is likely that larger doses would be required for pathogens with higher minimum inhibitory concentrations.

What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?

OBJECTIVES: The objectives of this study were to determine the effects of obesity on unbound trough concentrations and on the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets of piperacillin and meropenem in critically ill patients. METHODS: This study retrospectively analysed therapeutic-drug-monitoring data from ICU databases in Australia, Germany and Spain, as well as from a large PK study. The presence of obesity was defined as a BMI ≥30 kg/m(2), and patients were also categorized based on level of renal function. The presence of obesity was compared with unbound piperacillin and meropenem trough concentrations. We also used logistic regression to describe factors associated with the achievement of the PK/PD targets, an unbound concentration maintained above the MIC breakpoint (100% fT>MIC and 100% fT>4×MIC) of Pseudomonas aeruginosa. RESULTS: In all, 1400 patients were eligible for inclusion in the study. The median age and weight were 67 years (IQR 52-76 years) and 79 kg (69-90 kg), respectively, and 65% of participants were male. Significantly lower median piperacillin trough concentrations [29.4 mg/L (IQR 17.0-58.0 mg/L)] were found in obese patients compared with non-obese patients [42.0 mg/L (21.5-73.5 mg/L)] (P = 0.001). There was no difference for meropenem trough concentrations [obese 10.3 mg/L (IQR 4.8-16.0 mg/L) versus non-obese 11.0 mg/L (4.3-18.5 mg/L); P = 0.296]. Using logistic regression, we found that the presence of obesity was not associated with achievement of 100% fT>MIC, but the use of prolonged infusion, a creatinine clearance ≤100 mL/min, increasing age and female gender were for various PK/PD targets for both piperacillin and meropenem (P < 0.05). CONCLUSIONS: This large dataset has shown that the presence of obesity in critically ill patients may affect piperacillin, but not meropenem, unbound trough concentrations.

Mucinous cystadenoma of the ovary in a 12-year-old girl.

Benign mucinous cystadenomas MCA are rare benign neoplasms in the pediatric age group. Only 19 cases have been described before, and they often present as large abdominal masses. We present a 12-year-old patient that had a huge mass arising from the left ovary causing bilateral hydronephrosis and renal insufficiency. The final pathology revealed a benign MCA. Patients with mucinous tumors usually present late, this may lead to renal insufficiency secondary to urinary outflow obstruction. Unilateral salpingo-oophorectomy is usually sufficient treatment for these cases. The diagnosis of MCA should be considered in children who present with huge pelvi-abdominal masses. Early recognition and intervention are necessary to avoid potential complications.